Characterization of the molecular mechanism in RIAD Tg phenotype
1. The RIAD transgenic mouse model has in earlier studies showed an obese phenotype. Nevertheless, they maintain their metabolic integrity compared to other obese mouse models. As the transgenic modification only affects cells of the immune system, this project aims at clarifying the contribution of these and other cells in development of the phenotype. In addition, a more thorough metabolic profiling and behavioral studies will be performed.
2. This project will include bone marrow transplantation and surgical procedures. Although proper anesthesia and analgesia will be applied, we evaluate the stress to be moderate.
3. Negative metabolic changes (e.g. liver steatosis, insulin resistance, atherosclerosis etc.) are usually associated with obesity. However, the RIAD transgenic modification appears to protect the mice from developing these unfavorable changes. Our findings can therefore pave the way for novel therapeutic approaches in treating obesity-related metabolic complications.
4. Mus musculus, 1076 mice (223 RIAD transgenic, 223 littermates, 295 ApoE KO, 295 ApoE KO/RIAD transgenic and 40 Rag2 KO mice).
5. The interplay between individual cells, tissues and organs, and their obvious impact on the whole organism and its phenotype cannot be properly studied outside a living animal. Considerable individual variations are to be expected for metabolic studies in mice. The number of mice chosen for this project will allow us freedom to terminate animals showing discomfort, sickness or injuries without compromising the statistical validity of our study. The mice will be checked on a daily basis by KPM staff, and monitored on a weekly basis by project researchers. Anesthesia and analgesia will be properly administered when necessary, but we would like to emphasize that we will evaluate every case, and as a general rule rather terminate a suffering animal than expanding the period of analgesic treatment.
2. This project will include bone marrow transplantation and surgical procedures. Although proper anesthesia and analgesia will be applied, we evaluate the stress to be moderate.
3. Negative metabolic changes (e.g. liver steatosis, insulin resistance, atherosclerosis etc.) are usually associated with obesity. However, the RIAD transgenic modification appears to protect the mice from developing these unfavorable changes. Our findings can therefore pave the way for novel therapeutic approaches in treating obesity-related metabolic complications.
4. Mus musculus, 1076 mice (223 RIAD transgenic, 223 littermates, 295 ApoE KO, 295 ApoE KO/RIAD transgenic and 40 Rag2 KO mice).
5. The interplay between individual cells, tissues and organs, and their obvious impact on the whole organism and its phenotype cannot be properly studied outside a living animal. Considerable individual variations are to be expected for metabolic studies in mice. The number of mice chosen for this project will allow us freedom to terminate animals showing discomfort, sickness or injuries without compromising the statistical validity of our study. The mice will be checked on a daily basis by KPM staff, and monitored on a weekly basis by project researchers. Anesthesia and analgesia will be properly administered when necessary, but we would like to emphasize that we will evaluate every case, and as a general rule rather terminate a suffering animal than expanding the period of analgesic treatment.
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Obesity and cardiometabolic diseases are global health problems which are not completely understood.
In this project, the research group have studied a mouse model of T cell-induced obesity. RIAD transgenic mice are engineered to be protected from immunosuppression through the cAMP pathway in T cells. These mice have in earlier studies showed an obese phenotype, but without the negative metabolic changes usually associated with obesity.
The purpose of this project has been to assess the role of the altered immune cells and adipose tissue in RIAD transgenic mice in the development of this phenotype through multiple sub-studies.
1. Diet induced obesity and atherosclerosis. 2. Microbiota and immune cell function. 3. Fat distribution and adipose tissue function. 4. Blood pressure and heart function. 5. General behavior test.
During the study period, the researchers have shown by bone marrow transplantation and adaptive T cell transfer experiments, that this phenotype is actually driven by T cells.
Single cell RNA seq. analysis and CyTOF analysis have shown only minor alterations in circulating immune cells, however, suggesting more activated/exhausted t cells, which could be important for the phenotype. These are important new puzzle pieces to understand the role of immune cells in the development of these conditions.
Experiments have been executed successfully, resulting in new knowlegde about T cells in the regulation of obesity and cardiometabolic disease. These data have recently been published in iScience. (https://pubmed.ncbi.nlm.nih.gov/38551005/).
The project was approved for the use of up to 1076 mice.
The research focus in this project has been to characterize the function of immune cells in modulating obesity and metabolic pathways. Their role in atherosclerosis development was not assessed, resulting in the use of 0 atherogenic mice.
The total number of mice used in the project was 236.
144 mice have been reported with mild severity, 92 mice with moderate severity.
The responsible researcher informs that the development of ex vivo organoid systems is rapidly evolving, and such systems will in the future probably be important tools for the cardiometabolic research field. As of today, there are no such systems good enough to replace the mouse model to study the interplay between immune cells and development of cardiometabolic disease, in vivo.
The experimental design of this project was appropriate to address the research questions at hand, and complied to the best practice of refinement, reduction, and replacement (3Rs).
The humane endpoints were appropriate for this project.
In this project, the research group have studied a mouse model of T cell-induced obesity. RIAD transgenic mice are engineered to be protected from immunosuppression through the cAMP pathway in T cells. These mice have in earlier studies showed an obese phenotype, but without the negative metabolic changes usually associated with obesity.
The purpose of this project has been to assess the role of the altered immune cells and adipose tissue in RIAD transgenic mice in the development of this phenotype through multiple sub-studies.
1. Diet induced obesity and atherosclerosis. 2. Microbiota and immune cell function. 3. Fat distribution and adipose tissue function. 4. Blood pressure and heart function. 5. General behavior test.
During the study period, the researchers have shown by bone marrow transplantation and adaptive T cell transfer experiments, that this phenotype is actually driven by T cells.
Single cell RNA seq. analysis and CyTOF analysis have shown only minor alterations in circulating immune cells, however, suggesting more activated/exhausted t cells, which could be important for the phenotype. These are important new puzzle pieces to understand the role of immune cells in the development of these conditions.
Experiments have been executed successfully, resulting in new knowlegde about T cells in the regulation of obesity and cardiometabolic disease. These data have recently been published in iScience. (https://pubmed.ncbi.nlm.nih.gov/38551005/).
The project was approved for the use of up to 1076 mice.
The research focus in this project has been to characterize the function of immune cells in modulating obesity and metabolic pathways. Their role in atherosclerosis development was not assessed, resulting in the use of 0 atherogenic mice.
The total number of mice used in the project was 236.
144 mice have been reported with mild severity, 92 mice with moderate severity.
The responsible researcher informs that the development of ex vivo organoid systems is rapidly evolving, and such systems will in the future probably be important tools for the cardiometabolic research field. As of today, there are no such systems good enough to replace the mouse model to study the interplay between immune cells and development of cardiometabolic disease, in vivo.
The experimental design of this project was appropriate to address the research questions at hand, and complied to the best practice of refinement, reduction, and replacement (3Rs).
The humane endpoints were appropriate for this project.